Stereoselective Synthesis of 2‐Deoxy‐ β ‐ O ‐Aryl Glycosides by a One‐Pot Strategy Involving C─O Coupling and Catecholborane Reduction

Naturally occurring 2-deoxy-β-O-aryl glycosides are an important class of anticancer and antibacterial compounds. The direct glycosylation of phenols inevitably produces 2-deoxy-α-O-aryl glycosides, decreasing the efficiency of the synthesis of 2-deoxy-β-O-aryl glycosides. Herein we report a novel one-pot approach for the synthesis of 2-deoxy-β-O-aryl glycosides by the Cu(I)-catalyzed C─O cross-coupling reaction of 1-iodoglycals and phenols, followed by in situ reduction of the obtained ketene acetals with catecholborane. Starting from readily available materials, this protocol is applicable to a wide range of substrates, affording the corresponding 2-deoxy-β-O-aryl glycosides in high yields and with exclusive β-stereoselectivity. This strategy was further applied to the late-stage modification of various bioactive natural products or drugs. The remarkable stereoselectivity was rationalized by the experimental and theoretical studies.